Propranolol is an effective drug for the treatment of some patients with ventricular arrhythmias, but the dose varies widely. We propose to investigate the pharmacokinetic and pharmacodynamic factors responsible. Factors causing variable free drug concentration will be investigated including alpha 1 acid glycoprotein concentrations, free fatty acids (both spontaneous and following heparin administration) as these are involved during the evolution of a myocardial infarction. Because heparin administration appears to displace propranolol from tissue binding sites, its effects on beta-blockade due to propranolol will be tested. Concerning pharmacodynamic factors, we will test whether plasma catecholamine concentrations will predict subsequent response to propranolol after i.v. and oral administration. Finally we will measure the electrophysiological effects of propranolol in relation to its free drug concentration. These studies should help place propranolol therapy on a more rational and individual basis.